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      Early Detection and Serial Monitoring of Anthracycline-Induced Cardiotoxicity Using T1-mapping Cardiac Magnetic Resonance Imaging: An Animal Study

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          Abstract

          A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2–4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity.

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          Most cited references 26

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          Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines.

          Cardiovascular (CV) toxicity is a potential short- or long-term complication of various anticancer therapies. Some drugs, such as anthracyclines or other biological agents, have been implicated in causing potentially irreversible clinically important cardiac dysfunction. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare but serious complications have been described, and longer follow-up is needed to determine the exact profile and outcomes of related cardiac side-effects. Some of these side-effects are irreversible, leading to progressive CV disease, and some others induce reversible dysfunction with no long-term cardiac damage to the patient. Assessment of the prevalence, type and severity of cardiac toxicity caused by various cancer treatments is a breakthrough topic for patient management. Guidelines for preventing, monitoring and treating cardiac side-effects are a major medical need. Efforts are needed to promote strategies for cardiac risk prevention, detection and management, avoiding unintended consequences that can impede development, regulatory approval and patient access to novel therapy. These new ESMO Clinical Practice Guidelines are the result of a multidisciplinary cardio-oncology review of current evidence with the ultimate goal of providing strict criteria-based recommendations on CV risk prevention, assessment, monitoring and management during anticancer treatment.
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            ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography).

             ,  G Gregoratos,   (2003)
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              Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology.

              Conventional late gadolinium enhancement (LGE) cardiac magnetic resonance can detect myocardial infarction and some forms of non-ischaemic myocardial fibrosis. However, quantitative imaging of extracellular volume fraction (ECV) may be able to detect subtle abnormalities such as diffuse fibrosis or post-infarct remodelling of remote myocardium. The aims were (1) to measure ECV in myocardial infarction and non-ischaemic myocardial fibrosis, (2) to determine whether ECV varies with age, and (3) to detect sub-clinical abnormalities in 'normal appearing' myocardium remote from regions of infarction. Cardiac magnetic resonance ECV imaging was performed in 126 patients with T1 mapping before and after injection of gadolinium contrast. Conventional LGE images were acquired for the left ventricle. In patients with a prior myocardial infarction, the infarct region had an ECV of 51 ± 8% which did not overlap with the remote 'normal appearing' myocardium that had an ECV of 27 ± 3% (P < 0.001, n = 36). In patients with non-ischaemic cardiomyopathy, the ECV of atypical LGE was 37 ± 6%, whereas the 'normal appearing' myocardium had an ECV of 26 ± 3% (P < 0.001, n = 30). The ECV of 'normal appearing' myocardium increased with age (r = 0.28, P = 0.01, n = 60). The ECV of 'normal appearing' myocardium remote from myocardial infarctions increased as left ventricular ejection fraction decreased (r = -0.50, P = 0.02). Extracellular volume fraction imaging can quantitatively characterize myocardial infarction, atypical diffuse fibrosis, and subtle myocardial abnormalities not clinically apparent on LGE images. Taken within the context of prior literature, these subtle ECV abnormalities are consistent with diffuse fibrosis related to age and changes remote from infarction.
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                Author and article information

                Contributors
                bchoi@yuhs.ac
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 June 2017
                1 June 2017
                2017
                : 7
                Affiliations
                [1 ]ISNI 0000 0004 0636 3064, GRID grid.415562.1, Department of Radiology and Research Institute of Radiological Science, , Severance Hospital, Yonsei University Medical Centre, ; Seoul, South Korea
                [2 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Pathology, Gangnam Severance Hospital, , Yonsei University College of Medicine, ; Seoul, South Korea
                [3 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, , Yonsei University Medical Centre, ; Seoul, South Korea
                [4 ]ISNI 0000 0004 0532 8339, GRID grid.258676.8, Department of Veterinary Surgery, College of Veterinary Medicine, , Konkuk University, ; Seoul, South Korea
                [5 ]Siemens Ltd., Seoul, South Korea
                Article
                2627
                10.1038/s41598-017-02627-x
                5453985
                28572614
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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